This project focuses upon two features of the biology of class II histocompatibility antigens in experiments employing mice. These antigens, which are determined by genes in the Ia region of the Major Histocompatibility Complex, are of central importance to the induction of rejection reactions against transplants. They are richly represented on certain interstitial, bone marrow derived cells called "dendritic" cells. Evidence available suggests that eliminating or inactivating dendritic cells in donor tissues will greatly reduce rejection reactions. We can identify cells bearing Ia antigens in tissue sections using appropriate monoclonal antibodies and immunoperoxidase staining techniques. We will test a number of treatments designed to inactivate donor dendritic cells and will evaluate their success by direct observation of changes in dendritic cells in tissue samples and by transplant survival. Treatments will be administered either to intact donors or, by perfusion techniques, to hearts and kidneys after removal for transplantation by microsurgical techniques. Agents employed will include: monoclonal antibody to appropriate Ia antigens, fluorocarbons, cyclophosphamide, and irradiation. Our second line of investigation will be to expand upon our recent discovery that large quantities of newly detectable Ia antigens are produced in mouce kidneys transplanted to allogeneic recipients, especially in tubular cells, within a few days. The immunogenetic requirements, importance to transplant rejection, and mechanism (especially the involvement of Gamma-interferon) of this remarkable phenomenon will be investigated.